scholarly journals Tocilizumab is Associated with Increased Risk of Fungal Infections Among Critically Ill Patients with COVID-19 and Acute Renal Failure: An Observational Cohort Study.

Author(s):  
Barrett J Burger ◽  
Sarenthia M. Epps ◽  
Victor M. Cardenas ◽  
Rajani Jagana ◽  
Nikhil K. Meena ◽  
...  

Abstract Research QuestionDoes treatment with tocilizumab increase the risk of a fungal infection in critically ill patients with coronavirus-19?BackgroundNumerous therapies have been re-evaluated as possible treatment options for coronavirus-2019 caused by severe acute respiratory syndrome coronavirus-2. Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 receptor that has been proposed as a therapy for patients with severe coronavirus-19 pneumonia. The immunomodulatory effects of tocilizumab may have the unintended consequence of predisposing recipients to secondary infections. We sought to assess the risk of invasive fungal disease and the therapeutic impact of tocilizumab on hospital length of stay, duration of mechanical ventilation, and intensive care unit length of stay in critically ill patients with severe coronavirus-19.MethodsRecords of critically ill patients with coronavirus-2019 admitted from March to September 2020 at our institution were reviewed. The risk for fungal infections, intensive care unit length of stay, hospital length of stay, and duration of mechanical ventilation in those that received tocilizumab in addition to standard coronavirus-2019 treatments was assessed. ResultsFifty-six critically ill patients treated with dexamethasone and remdesivir for coronavirus-2019 were included, of which 16 patients also received tocilizumab. The majority of the cohort was African American, Asian, or other ethnic minorities (53.6%). Invasive fungal infections occurred in 10.7% of all patients and infection rates were significantly higher in the tocilizumab group than in the control group (31.2% vs 2.5%, Risk Difference [RD]= 28.8%, p<0.01). The increased risk in the tocilizumab group was strongly associated with renal replacement therapy. There was a dose-response relation between the risk of fungal infection and doses of tocilizumab, with 2.5% of infections occurring with zero doses, 20% with a single dose (RD=17.5%), and 50% with two doses (RD=47.5%) (trend test p<0.001). In addition, ICU LOS (23.4 days v 9.0 days, p <0.01), duration of mechanical ventilation (18.9 v. 3.5 days, p=0.01), and hospital LOS (29.1 v. 15.5, p <0.01) were increased in patients that received tocilizumab. ConclusionsRepurposed therapies, such as tocilizumab, may have a role in the treatment of severe coronavirus-2019 pneumonia but safety concerns remain. In this cohort, tocilizumab treatment was associated with an increased risk of fungal infection in those that were critically ill and received renal replacement therapy. Tocilizumab was also associated with increased ICU and hospital LOS and duration of mechanical ventilation.

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S346-S346
Author(s):  
Sarah Norman ◽  
Sara Jones ◽  
David Reeves ◽  
Christian Cheatham

Abstract Background At the time of this writing, there is no FDA approved medication for the treatment of COVID-19. One medication currently under investigation for COVID-19 treatment is tocilizumab, an interleukin-6 (IL-6) inhibitor. It has been shown there are increased levels of cytokines including IL-6 in severe COVID-19 hospitalized patients attributed to cytokine release syndrome (CRS). Therefore, inhibition of IL-6 receptors may lead to a reduction in cytokines and prevent progression of CRS. The purpose of this retrospective study is to utilize a case-matched design to investigate clinical outcomes associated with the use of tocilizumab in severe COVID-19 hospitalized patients. Methods This was a retrospective, multi-center, case-matched series matched 1:1 on age, BMI, and days since symptom onset. Inclusion criteria included ≥ 18 years of age, laboratory confirmed positive SARS-CoV-2 result, admitted to a community hospital from March 1st – May 8th, 2020, and received tocilizumab while admitted. The primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay, total mechanical ventilation days, mechanical ventilation mortality, and incidence of secondary bacterial or fungal infections. Results The following results are presented as tocilizumab vs control respectively. The primary outcome of in-hospital mortality for tocilizumab (n=26) vs control (n=26) was 10 (38%) vs 11 (42%) patients, p=0.777. The median hospital length of stay for tocilizumab vs control was 14 vs 11 days, p=0.275. The median days of mechanical ventilation for tocilizumab (n=21) vs control (n=15) was 8 vs 7 days, p=0.139, and the mechanical ventilation mortality was 10 (48%) vs 9 (60%) patients, p=0.463. In the tocilizumab group, for those expired (n=10) vs alive (n=16), 10 (100%) vs 7 (50%) patients respectively had a peak ferritin &gt; 600 ng/mL, and 6 (60%) vs 8 (50%) patients had a peak D-dimer &gt; 2,000 ng/mL. The incidence of secondary bacterial or fungal infections within 7 days of tocilizumab administration occurred in 5 (19%) patients. Conclusion These findings suggest that tocilizumab may be a beneficial treatment modality for severe COVID-19 patients. Larger, prospective, placebo-controlled trials are needed to further validate results. Disclosures Christian Cheatham, PharmD, BCIDP, Antimicrobial Resistance Solutions (Shareholder)


2020 ◽  
pp. 088506662094027
Author(s):  
Jeremy Cheuk Kin Sin ◽  
Lillian King ◽  
Emma Ballard ◽  
Stacey Llewellyn ◽  
Kevin B. Laupland ◽  
...  

Purpose: Hypophosphatemia is reported in up to 5% of hospitalized patients and ranges from 20% to 80% in critically ill patients. The consequences of hypophosphatemia for critically ill patients remain controversial. We evaluated the effect of hypophosphatemia on mortality and length of stay in intensive care unit (ICU) patients. Methods: MEDLINE, EMBASE, Cochrane Library (Reviews and Trials), and PubMed were searched for articles in English. The primary outcome was mortality and secondary outcome was length of stay. The quality of evidence was graded using a modified Newcastle-Ottawa Scale. Results: Our search yielded 828 articles and ultimately included 12 studies with 7626 participants in the analysis. Hypophosphatemia was associated with increased hospital length of stay (2.19 days [95% CI, 1.74-2.64]) and ICU length of stay (2.22 days [95% CI, 1.00-3.44]) but not mortality (risk ratio: 1.13 [95% CI, 0.98-1.31]; P = .09). Conclusions: Hypophosphatemia in ICU was associated with increased hospital and ICU length of stay but not all-cause mortality. Hypophosphatemia appears to be a marker of disease severity. Limited number of available studies and varied study designs did not allow for the ascertainment of the effect of severe hypophosphatemia on patient mortality.


2017 ◽  
Vol 35 (3) ◽  
pp. 257-263 ◽  
Author(s):  
Teresa Poon ◽  
Daryl Glick Paris ◽  
Samuel L. Aitken ◽  
Paru Patrawalla ◽  
Eric Bondarsky ◽  
...  

Background: Previous literature has suggested that a short course of corticosteroids is similarly effective as an extended course for managing an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, there are limited data regarding the optimal corticosteroid regimen in critically ill patients and the dosing strategies remain highly variable in this population. Methods: This retrospective cohort study evaluated patients with AECOPD admitted to the intensive care unit within a 2-year period. Patients were divided into short-course (≤5 days) or extended-course (>5 days) corticosteroid taper groups. The primary end point was treatment failure, defined as the need for intubation, reintubation, or noninvasive mechanical ventilation. Secondary end points included the duration of mechanical ventilation, hospital and intensive care unit length of stay, and adverse events. Results: Of the 151 patients who met the inclusion criteria, 94 received an extended taper and 57 received a short taper. Treatment failure occurred in 3 patients, who were all in the extended taper group ( P = .17). In a propensity score-matched cohort, the hospital length of stay was 7 days in the short taper group compared to 11 days in the extended taper group ( P < .0001). No differences in adverse events were observed. Conclusion: A short-course corticosteroid taper in critically ill patients with AECOPD is associated with reduced hospital length of stay and decreased corticosteroid exposure without increased risk of treatment failure. A prospective randomized trial is warranted.


2013 ◽  
Vol 32 ◽  
pp. S128
Author(s):  
M. Castro ◽  
C. Antunes ◽  
K. Kawamura ◽  
L.M. Horie ◽  
F.S. de Souza ◽  
...  

Author(s):  
Oliver Malle ◽  
Dietmar Maurer ◽  
Doris Wagner ◽  
Christian Schnedl ◽  
Steven Amrein ◽  
...  

Summary Background Sarcopenia, defined as loss of muscle mass, quality and function, is a part of the frailty syndrome. In critical illness, sarcopenia has rarely been evaluated regarding clinical outcomes. Therefore, we evaluated the association of sarcopenia with both hospital length of stay (HLOS) and 6‑month mortality in critically ill patients using abdominal computed tomography (CT) scans. Methods In a post hoc analysis from the high dose vitamin D3 vs. placebo in adult vitamin D deficient patients (VITdAL-ICU) trial, we retrospectively reviewed all available abdominal CT scans (18 women, 19 men). We measured and calculated total psoas area (TPA), psoas muscle density (PMD), skeletal muscle index (SMI) and bone mineral density (BMD) and analyzed the relation of these endpoints with HLOS and mortality. Defining sarcopenia we used cut-off values for TPA as 642.1 mm2/m2 in women and 784 mm2/m2 in men and PMD as 31.1 Hounsfield units (HU) in women and 33.3 HU in men, both measured at the level of L3, as well as for SMI (38.5 cm2/m2 in women and 52.4 cm2/m2 in men). Likely osteoporosis was defined by L1 trabecular attenuation of ≤110 HU. Values for TPA, PMD and SMI could not be obtained in 11 patients and BMD in 1 patient. Results Mean adjusted TPA was lower in women versus men (478 vs. 749 mm2/m2) as well as PMD (34.6 vs. 41.3 HU), SMI (62.36 vs. 76.81 cm2/m2) and BMD (141.1 vs. 157.2 HU). No significant influence on hospital length of stay and on 6‑month mortality was found, irrespective of the morphometric parameter used (TPA, PMD, SMI, BMD; p > 0.05). Survivors showed statistically nonsignificantly better values than nonsurvivors: TPA: 652 vs. 530 mm2/m2 (p = 0.27); PMD: 38.4 vs. 37.4 HU (p = 0.85); SMI: 70.32 vs. 69.54 cm2/m2 (p = 0.91); BMD: 156 vs. 145.8 HU (p = 0.81). Conclusion Although the study is limited by the small sample size, our data do not support a strong predictive value for TPA/PMD/SMI or BMD for HLOS or mortality in critically ill patients with vitamin D deficiency.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Claudia Dziegielewski ◽  
Charlenn Skead ◽  
Toros Canturk ◽  
Colleen Webber ◽  
Shannon M. Fernando ◽  
...  

Purpose. Delirium frequently affects critically ill patients in the intensive care unit (ICU). The purpose of this study is to evaluate the impact of delirium on ICU and hospital length of stay (LOS) and perform a cost analysis. Materials and Methods. Prospective studies and randomized controlled trials of patients in the ICU with delirium published between January 1, 2015, and December 31, 2020, were evaluated. Outcome variables including ICU and hospital LOS were obtained, and ICU and hospital costs were derived from the respective LOS. Results. Forty-one studies met inclusion criteria. The mean difference of ICU LOS between patients with and without delirium was significant at 4.77 days ( p < 0.001 ); for hospital LOS, this was significant at 6.67 days ( p < 0.001 ). Cost data were extractable for 27 studies in which both ICU and hospital LOS were available. The mean difference of ICU costs between patients with and without delirium was significant at $3,921 ( p < 0.001 ); for hospital costs, the mean difference was $5,936 ( p < 0.001 ). Conclusion. ICU and hospital LOS and associated costs were significantly higher for patients with delirium, compared to those without delirium. Further research is necessary to elucidate other determinants of increased costs and cost-reducing strategies for critically ill patients with delirium. This can provide insight into the required resources for the prevention of delirium, which may contribute to decreasing healthcare expenditure while optimizing the quality of care.


JAMA ◽  
2014 ◽  
Vol 312 (15) ◽  
pp. 1520 ◽  
Author(s):  
Karin Amrein ◽  
Christian Schnedl ◽  
Alexander Holl ◽  
Regina Riedl ◽  
Kenneth B. Christopher ◽  
...  

2016 ◽  
Vol 82 (10) ◽  
pp. 867-871 ◽  
Author(s):  
Ara Ko ◽  
Megan Y. Harada ◽  
Eric J.T. Smith ◽  
Michael Scheipe ◽  
Rodrigo F. Alban ◽  
...  

Elderly trauma patients may be at increased risk for underassessment and inadequate pain control in the emergency department (ED). We sought to characterize risk factors for oligoanalgesia in the ED in elderly trauma patients and determine whether it impacts outcomes in elderly trauma patients. We included elderly patients (age ≥55 years) with Glasgow Coma Scale scores 13 to 15 and Injury Severity Score (ISS) ≥9 admitted through the ED at a Level I trauma center. Patient characteristics and outcomes were compared between those who reported pain and received analgesics medication in the ED (MED) and those who did not (NO MED). A total of 183 elderly trauma patients were identified over a three-year study period, of whom 63 per cent had pain assessed via verbal pain score; of those who reported pain, 73 per cent received analgesics in the ED. The MED and NO MED groups were similar in gender, race, ED vitals, ISS, and hospital length of stay. However, NO MED was older, with higher head Abbreviated Injury Scale score and longer intensive care unit length of stay. Importantly, as patients aged they reported lower pain and were less likely to receive analgesics at similar ISS. Risk factors for oligoanalgesia may include advanced age and head injury.


2020 ◽  
pp. 088506662093379
Author(s):  
Emily J. Witcraft ◽  
Jeffrey P. Gonzales ◽  
Hyunuk Seung ◽  
Ian Watt ◽  
Asha L. Tata ◽  
...  

Purpose: Opioids are one of the high-risk medication classes that are administered to critically ill patients during their intensive care unit (ICU) stay. However, little attention has been given to inpatient opioid prescribing practices, especially in critically ill patients. The purpose of our study was to characterize opioid prescribing practices across 2 transitions of care during an inpatient hospital stay: medical ICU (MICU)/intermediate care unit (IMC) to floor and floor to hospital discharge and identify potential patient-specific factors that impact opioid continuation. Methods: This is a retrospective cohort study evaluating opioid-naive adult patients with new opioid therapy initiated in MICU/IMC at a tertiary care academic medical center from December 1, 2016, to November 30, 2017. Opioid continuation rate was assessed twice: transition 1 (MICU/IMC to floor) and transition 2 (floor to hospital discharge). Results: In total, 112 opioid-naive patients with initial opioid administration in the MICU/IMC were included. Opioid therapy was continued in 56.1% (37/66) at transition 1 and 56.8% of patients (21/37) at transition 2. Patients with opioids continued at transition 1 had a longer hospital length of stay compared to those not continued on opioids, 22 (interquartile range [IQR] 11-36) vs 8 (IQR 6-14; P = .0004). Among the patients continued on opioids at hospital discharge, intubation during hospital stay and cumulative opioid dosage were greater than those not continued on opioids (17 [80.9%] vs 7 [43.8%], P = .019; and 3482 mcg [IQR 1690-9530] vs 732.5 mcg [IQR 187.5-1360.9], P = .0018, respectively). Conclusions: Opioid-naive patients receiving opioid therapy in the MICU/IMC had a continuation rate of >56% during transitions of care, including hospital discharge. Factors that contributed to the continuation of opioids at transitions of care included longer hospital length of stay, intubation, and cumulative hospital opioid dosage. These findings may help to provide health systems with guidance on targeted opioid stewardship programs.


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